DESCRIPTION, OVERALL (provided by applicant): We propose a coordinated, highly interactive multidisciplinary collaboration between four Projects and two Cores with the main goal of making shock wave lithotripsy (SWL) safe and effective for all patients. In this work we will: Determine the chronic effects of SWL on the kidney-the long-term effects on renal structure and function that follow induction of acute damage during a treatment session Determine if lithotripsy induces new-onset diabetes Develop treatment protocols that protect patients from SWL adverse effects Determine the properties of SWs at their site of action in the kidney and proximal ureter Increase the efficiency of SWL by improving the acoustic coupling between the lithotripter and the patient Devise treatment protocols that improve SWL outcomes for obese patients Determine the treatment threshold for SWL injury and develop a method to monitor onset of conditions that are damaging to the kidney Evaluate the efficacy and safety of a new trend-low-pressure wide-focal-zone-in clinical lithotripter technology Develop acoustic monitoring and feedback techniques to improve the targeting and firing of lithotripters to eliminate the delivery of SWs that miss the stone, and to determine when the stone has broken to completion and the session can be ended Determine the mechanism by which cavitation within a vessel causes hemorrhage Develop numerical models to understand the role of cavitation and non-cavitational mechanisms in causing tissue damage PUBLIC HEALTH RELEVANCE: Shock wave lithotripsy (SWL) is the most common treatment used to remove renal stones. However, SWL has been found to cause acute trauma to the kidney and surrounding organs that is linked to potentially very serious chronic adverse effects. The proposed research will find ways to make SWL safer and more effective.